Herpesviruses and papillomaviruses can be found in a number of human malignant diseases, and are believed to play a significant role in the development of the tumors. This project will examine tissue from patients with oral cancer and leukoplakia in order to determine the role of oncogenic human DNA viruses in these conditions. The specific aims are: 1. To determine whether some oral leukoplakias and other soft tissue diseases are associated with specific viruses which can be identified, 2. To find evidence for the hypothesis that an interaction between herpesviruses and papillomaviruses is responsible for the development of some leukoplakias or oral cancers, and 3. To determine whether the response to treatment and the five-year survival rates of patients with oral cancer can be predicted from virological studies of the tumor. The viruses to be used are herpes simplex types 1 and 2, Epstein-Barr virus and human papillomaviruses types 1, 2, 4, 6, 11, 16 and 18. The techniques to be used include ELISA and radioimmunoassay of anti-virus antibody in patients' sera, immunoperoxidase staining of tumor tissue for the presence of viral antigen, and nucleic acid hybridization both in situ and on nitrocellulose filters to detect the presence of viral DNA. Viral antigens and DNA will be detected in preserved tissues which are available from earlier studies. One study followed 257 patients with leukoplakia, of whom 45 developed carcinoma, and the other study followed 70 patients with oral cancer. Sera from these patients will be tested for the levels and types of viral antibodies. Fresh tissues and sera will also be obtained from patients with these conditions and data from fresh and preserved tissue will be compared. This study will increase understanding of the pathogenesis of oral cancer. It might lead to more rational treatment of patients with leukoplakia by indicating which cases are most likely to develop carcinoma, and might lead to more rational selection of treatment of oral cancer by indicating which tumors are likely to respond to therapy.